A theoretical conformational study of substituted o-anisamides as models of a class of dopamine antagonists

Abstract

Abstract The quantum mechanical PCILO method has been used to investigate the conformational behaviour of N-(2-aminoethyl)- and N-(2-dimethylaminoethyl)-o-anisamide, two model molecules of substituted benzamides. The molecules are shown to have only limited conformational freedom due to the presence of two intramolecular hydrogen bonds acting as conformational locks. The molecules in their preferred conformation are characterized by a distance between the centre of the aromatic ring and the nitrogen atom of almost 6 Å, i.e. almost 1 Å longer than in the fully extended dopamine conformers. Some implications at the receptor level of this topographical dissimilarity are discussed.